Analyses of Registration Bipolar Prophylaxis Trials to Develop New Study Designs This application addresses Challenge Area (05) Comparative Effectiveness Research (CER) and specific Challenge Topic 05-MH-102 Cost Effectiveness of Mental Health Interventions...researchers can conduct analyses of existing databases for systematic benefit/harm analyses or to compare interventions on "real life outcomes" such as level of functioning or acceptability, using meta-analytic methods by means of conducting a rigorous evaluation of the comparative effectiveness and overall impact of 7 different primary drugs employed in maintenance treatment of bipolar disorders. Additionally, Aim 1 addresses Challenge Area (04) Clinical Research and specific Challenge Topic 04-MH-102 Refining categories of clinical phenotypes for mental health research purposes. Maintenance studies over the past decade have largely been limited to samples highly enriched for the experimental drug, emphasize efficacy over safety and tolerability, and have high drop out rates. To provide methodologies which can facilitate the development of new evidence based interventions and to improve overall outcomes and reduce adverse effect burdens, the applicants plan novel research on data sets from 11 completed large, randomized, blinded, placebo controlled maintenance trials. To validate concepts on remission, recovery, response, relapse, recurrence, subsyndromal symptoms and mood switch we shall test whether the concepts provide meaningful prediction of time to relapse/recurrence. Second, to test statistical techniques and outcome variables that incorporate different degrees of recovery, tolerability, adverse effects and functional status into integrated measures of bipolar outcomes, the applicants will develop measures that integrate results on efficacy, safety and function. Third, this research will identify illness characteristics which predict response to individual drugs and classes of drugs. This research will provide clinicians and patients with an evidence basis for considering safety and tolerability as equally important to efficacy in selecting and continuing a treatment. Results which these analyses would yield on valid clinical status criteria, integrative measures of outcome and predictors of response all serve to provide more efficient, earlier and more successful interventions, In implementation of initial and subsequent adjunctive regimens which are personalized to the characteristics of the patient and value tolerability as highly as efficacy. PUBLIC HEALTH RELEVANCE: These analyses of the major maintenance studies of bipolar disorder conducted over the past decade have the potential to empower care givers, patients and policy makers. The results will provide a unique and rigorous evaluation of the comparative effectiveness of current options available for maintenance treatment of bipolar disorders. Valuing tolerability as highly as efficacy will result in major public health benefits.